The 50 most-cited articles in Journal of Clinical Medicine, 2018

Vitamin A (VitA) is a micronutrient that is crucial for maintaining vision, promoting growth and development, and protecting epithelium and mucus integrity in the body. VitA is known as an anti-inflammation vitamin because of its critical role in enhancing immune function. VitA is involved in the development of the immune system and plays regulatory roles in cellular immune responses and humoral immune processes. VitA has demonstrated a therapeutic effect in the treatment of various infectious diseases. To better understand the relationship between nutrition and the immune system, the authors review recent literature about VitA in immunity research and briefly introduce the clinical application of VitA in the treatment of several infectious diseases.

For cognitive processes to function well, it is essential that the brain is optimally supplied with oxygen and blood. In recent years, evidence has emerged suggesting that cerebral oxygenation and hemodynamics can be modified with physical activity. To better understand the relationship between cerebral oxygenation/hemodynamics, physical activity, and cognition, the application of state-of-the art neuroimaging tools is essential. Functional near-infrared spectroscopy (fNIRS) is such a neuroimaging tool especially suitable to investigate the effects of physical activity/exercises on cerebral oxygenation and hemodynamics due to its capability to quantify changes in the concentration of oxygenated hemoglobin (oxyHb) and deoxygenated hemoglobin (deoxyHb) non-invasively in the human brain. However, currently there is no clear standardized procedure regarding the application, data processing, and data analysis of fNIRS, and there is a large heterogeneity regarding how fNIRS is applied in the field of exercise⁻cognition science. Therefore, this review aims to summarize the current…

BACKGROUND: Drug-induced interstitial lung disease (DIILD) occurs as a result of numerous agents, but the risk often only becomes apparent after the marketing authorisation of such agents. METHODS: In this PRISMA-compliant systematic review, we aimed to evaluate and synthesise the current literature on DIILD. RESULTS: Following a quality assessment, 156 full-text papers describing more than 6000 DIILD cases were included in the review. However, the majority of the papers were of low or very low quality in relation to the review question (78%). Thus, it was not possible to perform a meta-analysis, and descriptive review was undertaken instead. DIILD incidence rates varied between 4.1 and 12.4 cases/million/year. DIILD accounted for 3⁻5% of prevalent ILD cases. Cancer drugs, followed by rheumatology drugs, amiodarone and antibiotics, were the most common causes of DIILD. The radiopathological phenotype of DIILD varied between and within agents, and no typical radiological pattern specific to DIILD was identified. Mortality rates of over 50% were reported in some studies. Severity at…

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterised by chronic, progressive scarring of the lungs and the pathological hallmark of usual interstitial pneumonia. Current paradigms suggest alveolar epithelial cell damage is a key initiating factor. Globally, incidence of the disease is rising, with associated high morbidity, mortality, and economic healthcare burden. Diagnosis relies on a multidisciplinary team approach with exclusion of other causes of interstitial lung disease. Over recent years, two novel antifibrotic therapies, pirfenidone and nintedanib, have been developed, providing treatment options for many patients with IPF, with several other agents in early clinical trials. Current efforts are directed at identifying key biomarkers that may direct more customized patient-centred healthcare to improve outcomes for these patients in the future.

Social media enables the public sharing of information. With the recent emphasis on transparency and the open sharing of information between doctors and patients, the intersection of social media and healthcare is of particular interest. Twitter is currently the most popular form of social media used for healthcare communication; here, we examine the use of Twitter in medicine and specifically explore in what capacity using Twitter to share information on treatments and research has the potential to improve care. The sharing of information on Twitter can create a communicative and collaborative atmosphere for patients, physicians, and researchers and even improve quality of care. However, risks involved with using Twitter for healthcare discourse include high rates of misinformation, difficulties in verifying the credibility of sources, overwhelmingly high volumes of information available on Twitter, concerns about professionalism, and the opportunity cost of using physician time. Ultimately, the use of Twitter in healthcare can allow patients, healthcare professionals, and…

Islets of Langerhans are islands of endocrine cells scattered throughout the pancreas. A number of new studies have pointed to the potential for conversion of non-β islet cells in to insulin-producing β-cells to replenish β-cell mass as a means to treat diabetes. Understanding normal islet cell mass and function is important to help advance such treatment modalities: what should be the target islet/β-cell mass, does islet architecture matter to energy homeostasis, and what may happen if we lose a particular population of islet cells in favour of β-cells? These are all questions to which we will need answers for islet replacement therapy by transdifferentiation of non-β islet cells to be a reality in humans. We know a fair amount about the biology of β-cells but not quite as much about the other islet cell types. Until recently, we have not had a good grasp of islet mass and distribution in the human pancreas. In this review, we will look at current data on islet cells, focussing more on non-β cells, and on human pancreatic islet mass and distribution.

Head and neck squamous cell carcinomas (HNSCCs) arise in the mucosal lining of the upper aerodigestive tract. Tobacco and alcohol use have been reported to be associated with HNSCC. Infection with high-risk human papillomaviruses (HPVs) has recently been implicated in the pathogenesis of HNSCCs. It is now widely accepted that high-risk HPV is a cause of almost all cervical cancers as well as some forms of HNSCCs. HPV-related HNSCCs are increasing. HPV-related HNSCCs and HPV-unrelated HNSCCs differ with respect to the molecular mechanisms underlying their oncogenic processes. HPV-related HNSCCs are known to have a better prognosis response to treatment as compared with HPV-unrelated HNSCCs. Therefore, in recent years, it has been required to accurately discriminate between HPV-related and HPV-unrelated HNSCCs. To diagnose the HPV-related HNSCCs, various methods including P16 immunohistochemistry, FISH, and genetic analyses of the HPV gene from histopathological and liquid biopsy specimens have been employed. Based on the results of the differential diagnosis, various treatments…

Background: Heart rate variability (HRV) as an accurate, noninvasive measure of the Autonomous Nervous System (ANS) can reflect mental health (e.g., stress, depression, or anxiety). Tai Chi and Yoga (Tai Chi/Yoga), as the most widely practiced mind–body exercises, have shown positive outcomes of mental health. To date, no systematic review regarding the long-lasting effects of Tai Chi/Yoga on HRV parameters and perceived stress has been conducted. Objective: To critically evaluate the existing literature on this topic. Methods: Five electronic databases (Web of Science, PubMed, Scopus, SportDiscus and Cochrane Library) were searched from the start of the research project to July 2018. Study selection, data extraction, and study quality assessment were independently carried out by two reviewers. The potentially identified randomized controlled trials (RCT) reported the useful quantitative data that were included only for meta-analysis. Results: meta-analysis of 17 medium-to-high quality RCTs showed significantly beneficial effects on HRV parameters (normalized low-frequency, Hedge’s…

There have been few large-scale studies on the relationship between smoking and gut microbiota. We investigated the relationship between smoking status and the composition of gut microbiota. This was a population-based cross-sectional study using Healthcare Screening Center cohort data. A total of 758 men were selected and divided into three groups: never (n = 288), former (n = 267), and current smokers (n = 203). Among the three groups, there was no difference in alpha diversity, however, Jaccard-based beta diversity showed significant difference (p = 0.015). Pairwise permutational multivariate analysis of variance (PERMANOVA) tests between never and former smokers did not show a difference; however, there was significant difference between never and current smokers (p = 0.017) and between former and current smokers (p = 0.011). Weighted UniFrac-based beta diversity also showed significant difference among the three groups (p = 0.038), and pairwise PERMANOVA analysis of never and current smokers showed significant difference (p = 0.01). In the analysis of bacterial composition,…

Benzodiazepines are some of the most commonly prescribed medications in the world. These sedative-hypnotics can provide rapid relief for symptoms like anxiety and insomnia, but are also linked to a variety of adverse effects (whether used long-term, short-term, or as needed). Many patients take benzodiazepines long-term without ever receiving evidence-based first-line treatments (e.g., psychotherapy, relaxation techniques, sleep hygiene education, serotonergic agents). This review discusses the risks and benefits of, and alternatives to benzodiazepines. We discuss evidence-based indications and contraindications, and the theoretical biopsychosocial bases for effectiveness, ineffectiveness and harm. Potential adverse effects and drug-drug interactions are summarized. Finally, both fast-acting/acute and delayed-action/chronic alternative treatments for anxiety and/or insomnia are discussed. Response to treatment-whether benzodiazepines, other pharmacological agents, or psychotherapy-should be determined based on functional recovery and not merely sedation.

Exergaming, or active video gaming, has become an emerging trend in fitness, education and health sectors. It is defined as digital games that require bodily movements to play, stimulating an active gaming experience to function as a form of physical activity (PA). Since exergaming is becoming more popular, claims have been made on the usefulness of exergaming. It has, for example, been entitled as being "the future of fitness" by the American College of Sports Medicine, promoting PA and health in children and adolescents. However, research also suggests that long-term engagement in exergaming is difficult to achieve, and there is a noticeable reservation towards exergaming by parents, teachers and caregivers. To provide an overview and to outline the future directions of exergaming, the aim of this review was to critically illustrate the strengths, weaknesses, opportunities and threats of exergaming to promote PA and health in children and youth. The available evidence indicates that exergaming has the potential to improve health via an increase in PA. However, it seems that this…

Resting heart rate (RHR) is positively related with mortality. Regular exercise causes a reduction in RHR. The aim of the systematic review was to assess whether regular exercise or sports have an impact on the RHR in healthy subjects by taking different types of sports into account. A systematic literature research was conducted in six databases for the identification of controlled trials dealing with the effects of exercise or sports on the RHR in healthy subjects was performed. The studies were summarized by meta-analyses. The literature search analyzed 191 studies presenting 215 samples fitting the eligibility criteria. 121 trials examined the effects of endurance training, 43 strength training, 15 combined endurance and strength training, 5 additional school sport programs. 21 yoga, 5 tai chi, 3 qigong, and 2 unspecified types of sports. All types of sports decreased the RHR. However, only endurance training and yoga significantly decreased the RHR in both sexes. The exercise-induced decreases of RHR were positively related with the pre-interventional RHR and negatively with…

The C-reactive protein (CRP)/albumin ratio has recently emerged as a marker for poor prognosis or mortality across various patient groups. This study aimed to identify the association between CRP/albumin ratio and 28-day mortality and predict the accuracy of CRP/albumin ratio for 28-day mortality in medical intensive care unit (ICU) patients. This was a retrospective cohort study of 875 patients. We evaluated the prognostic value of CRP/albumin ratio to predict mortality at 28 days after ICU admission, using Cox proportional hazard model and Kaplan-Meier survival analysis. The 28-day mortality was 28.0%. In the univariate analysis, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score (p < 0.001), CRP level (p = 0.045), albumin level (p < 0.001), and CRP/albumin ratio (p = 0.032) were related to 28-day mortality. The area under the receiver operating characteristic (ROC) curve (the area under the ROC curves (AUC)) of CRP/albumin ratio was higher than that of CRP for mortality (0.594 vs. 0.567, p < 0.001). The cut-off point for CRP/albumin ratio for mortality was…

Nanoparticles are zero-dimensional nanomaterials and, based on their nature, they can be categorized into organic, inorganic, and composites nanoparticles. Due to their unique physical and chemical properties, nanoparticles are extensively used in a variety of fields, including medicine, pharmaceutics, and food industry. Although they have the potential to improve the diagnosis and treatment of brain diseases, it is fundamentally important to develop standardized toxicological studies, which can prevent the induction of neurotoxic effects. The focus of this review is to emphasize both the beneficial and negative effects of nanoparticles on brain health.

OBJECTIVE: Although current evidence supports the use of virtual reality (VR) in the treatment of mental disorders, it is unknown whether VR exercise would be beneficial to mental health. This review synthesized literature concerning the effect of VR exercise on anxiety and depression among various populations. METHODS: Ten electronic databases were searched for studies on this topic from January 2000 through October 2017. Studies were eligible if the article: (1) was peer-reviewed; (2) was published in English; and (3) used quantitative measures in assessing anxiety- and depression-related outcomes. RESULTS: A total of five empirical studies met the eligibility criteria. These studies included two randomized clinical trials, one control trial, and two cross-sectional studies. Four studies reported significant improvements in anxiety- and depression-related measures following VR exercise, including reduced tiredness and tension, in addition to increased energy and enjoyment. Nonetheless, one study failed to support the effectiveness of VR exercise over traditional exercise alone on…

Standard noninvasive methods for detecting renal allograft rejection and injury have poor sensitivity and specificity. Plasma donor-derived cell-free DNA (dd-cfDNA) has been reported to accurately detect allograft rejection and injury in transplant recipients and shown to discriminate rejection from stable organ function in kidney transplant recipients. This study used a novel single nucleotide polymorphism (SNP)-based massively multiplexed PCR (mmPCR) methodology to measure dd-cfDNA in various types of renal transplant recipients for the detection of allograft rejection/injury without prior knowledge of donor genotypes. A total of 300 plasma samples (217 biopsy-matched: 38 with active rejection (AR), 72 borderline rejection (BL), 82 with stable allografts (STA), and 25 with other injury (OI)) were collected from 193 unique renal transplant patients; dd- cfDNA was processed by mmPCR targeting 13,392 SNPs. Median dd-cfDNA was significantly higher in samples with biopsy-proven AR (2.3%) versus BL (0.6%), OI (0.7%), and STA (0.4%) (p < 0.0001 all comparisons). The SNP-based dd-cfDNA…

Acute kidney injury (AKI) after liver transplantation has been reported to be associated with increased mortality. Recently, machine learning approaches were reported to have better predictive ability than the classic statistical analysis. We compared the performance of machine learning approaches with that of logistic regression analysis to predict AKI after liver transplantation. We reviewed 1211 patients and preoperative and intraoperative anesthesia and surgery-related variables were obtained. The primary outcome was postoperative AKI defined by acute kidney injury network criteria. The following machine learning techniques were used: decision tree, random forest, gradient boosting machine, support vector machine, naïve Bayes, multilayer perceptron, and deep belief networks. These techniques were compared with logistic regression analysis regarding the area under the receiver-operating characteristic curve (AUROC). AKI developed in 365 patients (30.1%). The performance in terms of AUROC was best in gradient boosting machine among all analyses to predict AKI of all stages (0.90,…

Machine learning approaches were introduced for better or comparable predictive ability than statistical analysis to predict postoperative outcomes. We sought to compare the performance of machine learning approaches with that of logistic regression analysis to predict acute kidney injury after cardiac surgery. We retrospectively reviewed 2010 patients who underwent open heart surgery and thoracic aortic surgery. Baseline medical condition, intraoperative anesthesia, and surgery-related data were obtained. The primary outcome was postoperative acute kidney injury (AKI) defined according to the Kidney Disease Improving Global Outcomes criteria. The following machine learning techniques were used: decision tree, random forest, extreme gradient boosting, support vector machine, neural network classifier, and deep learning. The performance of these techniques was compared with that of logistic regression analysis regarding the area under the receiver-operating characteristic curve (AUC). During the first postoperative week, AKI occurred in 770 patients (38.3%). The best performance…

It is currently thought that extracellular vesicles (EVs), such as exosomes and microvesicles, play an important autocrine/paracrine role in intercellular communication. EVs package proteins, mRNA and microRNA (miRNA), which have the ability to transfer biological information to recipient cells in the lungs. Depending on their origin, EVs fulfil different functions. EVs derived from mesenchymal stem cells (MSCs) have been found to promote therapeutic activities that are comparable to MSCs themselves. Recent animal model-based studies suggest that MSC-derived EVs have significant potential as a novel alternative to whole-cell therapies. Compared to their parent cells, EVs may have a superior safety profile and can be stored without losing function. It has been observed that MSC-derived EVs suppress pro-inflammatory processes and reduce oxidative stress, pulmonary fibrosis and remodeling in a variety of in vivo inflammatory lung disease models by transferring their components. However, there remain significant challenges to translate this therapy to the clinic. From this view point,…

Background: Tai Chi, Qigong, and Yoga are recognized as the most popular complementary approaches for alleviating musculoskeletal pain, improving sleep quality, and reducing blood pressure. The therapeutic effects of these meditative movements for treating major depressive disorder (MDD) is yet to be determined. Therefore, we examined whether meditative movements (Tai Chi, Qigong, and Yoga) are effective for treating MDD. Seven electronic databases (SPORTDiscus, PubMed, PsycINFO, Cochrane Library, Web of Science, CNKI, and Wanfang) were used to search relevant articles. Randomized controlled trials (RCT) using Tai Chi, Qigong or Yoga as intervention for MDD were considered for the meta-analysis (standardized mean difference: SMD). Results: Meta-analysis on 15 fair-to-high quality RCTs showed a significant benefit in favor of meditative movement on depression severity (SMD = −0.56, 95% CI −0.76 to −0.37, p < 0.001, I2 = 35.76%) and on anxiety severity (SMD = −0.46, 95% CI −0.71 to −0.21, p < 0.001, I2 = 1.17%). Meditative movement interventions showed significantly improved treatment…

BACKGROUND: The purpose of this systematic review was to examine the association and directionality between mental health disorders and substance use among adolescents and young adults in the U.S. and Canada. METHODS: The following databases were used: Medline, PubMed, Embase, PsycINFO, and Cochrane Library. Meta-analysis used odds ratios as the pooled measure of effect. RESULTS: A total of 3656 studies were screened and 36 were selected. Pooled results showed a positive association between depression and use of alcohol (odds ratio (OR) = 1.50, 95% confidence interval (CI): 1.24⁻1.83), cannabis (OR = 1.29, 95% CI: 1.10⁻1.51), and tobacco (OR = 1.65, 95% CI: 1.43⁻1.92). Significant associations were also found between anxiety and use of alcohol (OR = 1.54, 95% CI: 1.19⁻2.00), cannabis (OR = 1.36, 95% CI: 1.02⁻1.81), and tobacco (OR = 2.21, 95% CI: 1.54⁻3.17). A bidirectional relationship was observed with tobacco use at baseline leading to depression at follow-up (OR = 1.87, CI = 1.23⁻2.85) and depression at baseline leading to tobacco use at follow-up (OR = 1.22, CI = 1.09⁻1.37). A…

A systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating the core components of cardiac rehabilitation (CR), nutritional counseling (NC), risk factor modification (RFM), psychosocial management (PM), patient education (PE), and exercise training (ET)) was undertaken. Published RCTs were identified from database inception dates to April 2017, and risk of bias assessed using Cochrane's tool. Endpoints included mortality (all-cause and cardiovascular (CV)) and morbidity (fatal and non-fatal myocardial infarction (MI), coronary artery bypass surgery (CABG), percutaneous coronary intervention (PCI), and hospitalization (all-cause and CV)). Meta-regression models decomposed treatment effects into the main effects of core components, and two-way or all-way interactions between them. Ultimately, 148 RCTs (50,965 participants) were included. Main effects models were best fitting for mortality (e.g., for all-cause, specifically PM (hazard ratio HR = 0.68, 95% credible interval CrI = 0.54⁻0.85) and ET (HR = 0.75, 95% CrI = 0.60⁻0.92) components…

Background: Although the third most frequent interstitial lung disease, hypersensitivity pneumonitis (HP) remains an enigmatic disease without clear diagnostic and therapeutic guidelines. We assessed the effect of the commonly used therapeutic interventions (i.e. exposure avoidance and corticosteroid treatment) in an HP cohort. Methods: We collected clinical data of all HP patients followed at our centre between January 1, 2005, and December 31, 2016. HP patients were stratified according to the presence of fibrosis on chest CT. Survival was analysed using the multivariate Cox proportional hazards model. Forced vital capacity (percent predicted, FVC%) and diffusing capacity of the lung for carbon monoxide (percent predicted, DLCO%) evolution were analysed using linear mixed-effect models. Results: Two hundred and two HP patients were identified: 93 non-fibrotic HP (nfHP) and 109 fibrotic HP (fHP), experiencing a monthly FVC% decline before treatment of 0.93% and 0.56%, respectively. While nfHP had an excellent survival, fHP patients experienced a median survival of 9.2 years.…

Children with Autism Spectrum Disorder (ASD) are at an increased risk for sleep disturbances, and studies indicate that between 50 and 80% of children with ASD experience sleep problems. These problems increase parental stress and adversely affect family quality of life. Studies have also suggested that sleep disturbances may increase behavioral problems in this clinical population. Although understanding the causes of sleep disorders in ASD is a clinical priority, the causal relationship between these two conditions remains unclear. Given the complex nature of ASD, the etiology of sleep problems in this clinical population is probably multi-factorial. In this overview, we discuss in detail three possible etiological explanations of sleep problems in ASD that can all contribute to the high rate of these symptoms in ASD. Specifically, we examine how neurobiological alterations, genetic mutations, and disrupted sleep architecture can cause sleep problems in individuals with ASD. We also discuss how sleep problems may be a direct result of core symptoms of ASD. Finally, a detailed…

Paragangliomas are neuroendocrine neoplasms, derived from paraganglia of the sympathetic and parasympathetic nervous systems. They are most commonly identified in the head and neck, being most frequent in the carotid body, followed by jugulotympanic paraganglia, vagal nerve and ganglion nodosum, as well as laryngeal paraganglia. Abdominal sites include the well-known urinary bladder tumors that originate in the Organ of Zuckerkandl. However, other unusual sites of origin include peri-adrenal, para-aortic, inter-aortocaval, and paracaval retroperitoneal sites, as well as tumors in organs where they may not be expected in the differential diagnosis of neuroendocrine neoplasms, such as thyroid, parathyroid, pituitary, gut, pancreas, liver, mesentery, lung, heart and mediastinum. The distinction of these lesions from epithelial neuroendocrine neoplasms is critical for several reasons. Firstly, the determination of clinical and biochemical features is different from that used for epithelial neuroendocrine tumors. Secondly, the genetic implications are different, since…

Cutaneous nerve entrapment plays an important role in neuropathic pain syndrome. Due to the advancement of ultrasound technology, the cutaneous nerves can be visualized by high-resolution ultrasound. As the cutaneous nerves course superficially in the subcutaneous layer, they are vulnerable to entrapment or collateral damage in traumatic insults. Scanning of the cutaneous nerves is challenging due to fewer anatomic landmarks for referencing. Therefore, the aim of the present article is to summarize the anatomy of the limb cutaneous nerves, to elaborate the scanning techniques, and also to discuss the clinical implications of pertinent entrapment syndromes of the medial brachial cutaneous nerve, intercostobrachial cutaneous nerve, medial antebrachial cutaneous nerve, lateral antebrachial cutaneous nerve, posterior antebrachial cutaneous nerve, superficial branch of the radial nerve, dorsal cutaneous branch of the ulnar nerve, palmar cutaneous branch of the median nerve, anterior femoral cutaneous nerve, posterior femoral cutaneous nerve, lateral femoral cutaneous nerve, sural nerve,…

WDR5 is a highly conserved WD40 repeat-containing protein that is essential for proper regulation of multiple cellular processes. WDR5 is best characterized as a core scaffolding component of histone methyltransferase complexes, but emerging evidence demonstrates that it does much more, ranging from expanded functions in the nucleus through to controlling the integrity of cell division. The purpose of this review is to describe the current molecular understandings of WDR5, discuss how it participates in diverse cellular processes, and highlight drug discovery efforts around WDR5 that may form the basis of new anti-cancer therapies.

The role of testosterone in the pathophysiology of inflammation is of critical clinical importance; however, no universal mechanism(s) has been advanced to explain the complex and interwoven pathways of androgens in the attenuation of the inflammatory processes. PubMed and EMBASE searches were performed, including the following key words: "testosterone", "androgens", "inflammatory cytokines", "inflammatory biomarkers" with focus on clinical studies as well as basic scientific studies in human and animal models. Significant benefits of testosterone therapy in ameliorating or attenuating the symptoms of several chronic inflammatory diseases were reported. Because anti⁻tumor necrosis factor therapy is the mainstay for the treatment of moderate-to-severe inflammatory bowel disease; including Crohn's disease and ulcerative colitis, and because testosterone therapy in hypogonadal men with chronic inflammatory conditions reduce tumor necrosis factor-alpha (TNF-α), IL-1β, and IL-6, we suggest that testosterone therapy attenuates the inflammatory process and reduces the burden of disease by…

The central nervous system (CNS) and the human gastrointestinal (GI) tract communicate through the gut-brain axis (GBA). Such communication is bi-directional and involves neuronal, endocrine, and immunological mechanisms. There is mounting data that gut microbiota is the source of a number of neuroactive and immunocompetent substances, which shape the structure and function of brain regions involved in the control of emotions, cognition, and physical activity. Most GI diseases are associated with altered transmission within the GBA that are influenced by both genetic and environmental factors. Current treatment protocols for GI and non-GI disorders may positively or adversely affect the composition of intestinal microbiota with a diverse impact on therapeutic outcome(s). Alterations of gut microbiota have been associated with mood and depressive disorders. Moreover, mental health is frequently affected in GI and non-GI diseases. Deregulation of the GBA may constitute a grip point for the development of diagnostic tools and personalized microbiota-based therapy. For example, next…

Physical exercise is effective for sarcopenic elderly but evidence for the most effective mode of exercise is conflicting. The objective of this study was to investigate the effects of a three-month group-based versus home-based exercise program on muscular, functional/physical performance and quality of life (QoL) across elderly with sarcopenia. 54 elderly (47 women, 7 men aged 72.87 ± 7 years) were randomly assigned to one of three interventions: supervised group (n = 18), individualized home-based exercise (n = 18) and control group (n = 18). Body composition was determined by bioelectrical impedance analysis, calf measurement with inelastic tape and strength assessments (grip and knee muscle strength) via hand-held and isokinetic dynamometers. Functional assessments included four-meter (4 m), Τimed-Up and Go (TUG) and chair stand (CS) tests. QoL was assessed with Greek Sarcopenia Quality of Life (SarQol_GR) questionnaire. Outcomes were assessed at baseline, immediately post-intervention (week 12), and 3 months post-intervention (week 24). Significant group x time interactions (p…

Acute vascular endothelial dysfunction is a central event in the pathogenesis of sepsis, increasing vascular permeability, promoting activation of the coagulation cascade, tissue edema and compromising perfusion of vital organs. Aging and chronic diseases (hypertension, dyslipidaemia, diabetes mellitus, chronic kidney disease, cardiovascular disease, cerebrovascular disease, chronic pulmonary disease, liver disease, or cancer) are recognized risk factors for sepsis. In this article we review the features of endothelial dysfunction shared by sepsis, aging and the chronic conditions preceding this disease. Clinical studies and review articles on endothelial dysfunction in sepsis, aging and chronic diseases available in PubMed were considered. The main features of endothelial dysfunction shared by sepsis, aging and chronic diseases were: (1) increased oxidative stress and systemic inflammation, (2) glycocalyx degradation and shedding, (3) disassembly of intercellular junctions, endothelial cell death, blood-tissue barrier disruption, (4) enhanced leukocyte adhesion and extravasation,…

BACKGROUND: Chronic kidney disease (CKD) is a global health threat affecting approximately 10% of the adult population worldwide. Multimorbidity is common in CKD, but its impacts on disease outcomes are seldom investigated. METHODS: This prospective cohort analysis followed patients, who were part of a multidisciplinary CKD care program, for 10 years. We aimed to determine the impact of multimorbidity on renal outcomes. RESULTS: Overall, 1463 patients with stage 3⁻5 CKD were enrolled and stratified by the number of comorbidities. Mean follow-up time was 6.39 ± 1.19 years. We found that stage 3⁻5 CKD patients with at least three comorbidities at enrollment initiated dialysis earlier (hazard ratio (HR): 2.971) than patients without comorbidities. Risk factors for multimorbidity included old age, smoking, and proteinuria. CONCLUSIONS: By analyzing the number of comorbidities, a simple and readily applicable method, we demonstrated an association between multimorbidity and poor renal outcomes in stage 3⁻5 CKD patients. In addition to current guideline-based approaches, our results…

The use of gamification in healthcare has been gaining popularity. This prospective, randomized, clinical trial was designed to evaluate whether gamification of the preoperative process—via virtual reality (VR) gaming that provides a vivid, immersive and realistic experience—could reduce preoperative anxiety in children. Seventy children scheduled for elective surgery under general anesthesia were randomly divided into either the control or gamification group. Children in the control group received conventional education regarding the preoperative process, whereas those in the gamification group played a 5 min VR game experiencing the preoperative experience. Preoperative anxiety, induction compliance checklist (ICC), and procedural behavior rating scale (PBRS) were measured. Sixty-nine children were included in the final analysis (control group = 35, gamification = 34). Preoperative anxiety (28.3 [23.3–36.7] vs. 46.7 [31.7–51.7]; p < 0.001) and intraoperative compliance measured using ICC (p = 0.038) were lower in the gamification group than in the control group. However, PBRS (p =…

Arterial Blood Pressure (ABP) and photoplethysmography (PPG) are both useful techniques to monitor cardiovascular status. Though ABP monitoring is more widely employed, this procedure of signal acquisition whether done invasively or non-invasively may cause inconvenience and discomfort to the patients. PPG, however, is simple, noninvasive, and can be used for continuous measurement. This paper focuses on analyzing the similarities in time and frequency domains between ABP and PPG signals for normotensive, prehypertensive and hypertensive subjects and the feasibility of the classification of subjects considering the results of the analysis performed. From a database with 120 records of ABP and PPG, each 120 s in length, the records where separated into epochs taking into account 10 heartbeats, and the following statistical measures were performed: Correlation (r), Coherence (COH), Partial Coherence (pCOH), Partial Directed Coherence (PDC), Directed Transfer Function (DTF), Full Frequency Directed Transfer Function (ffDTF) and Direct Directed Transfer Function (dDTF). The correlation…

Colorectal cancer (CRC) incidence rates have declined in recent years for people of all races/ethnicities; however, the extent to which the decrease varies annually by demographic and disease-related characteristics is largely unknown. This study examines trends and annual percent change (APC) in the incidence among persons diagnosed with CRC in the United States of America from 2000–2014. The data obtained from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program were analyzed, and all persons (N = 577,708) with malignant CRC recorded in the SEER 18 database from 2000 to 2014 were characterized according to sex, race, age at diagnosis, disease site and stage. Incidence rates and APC were calculated for the entire study period. Overall, the incidence rate of CRC decreased from 54.5 in 2000 to 38.6 per 100,000 in 2014, with APC = −2.66 (p < 0.0001). Decline in rates was most profound between 2008 and 2011 from 46.0 to 40.7 per 100,000 (APC = −4.04; p < 0.0001). Rates were higher for males (vs. females; rate ratio (RR) = 1.33) and for blacks (vs.…

By the sixth decade of life, nearly one quarter of the population has substantial muscle atrophy, or sarcopenia. Despite the creation of a standardized definition of sarcopenia by the European Working Group on Sarcopenia in Older People, variability may exist in the diagnostic criteria utilized for clinical sarcopenia research. The primary objectives of this review were to characterize diagnostic criteria used for measurement of sarcopenia in original studies, and to describe associations between sarcopenia and important clinical outcomes. We performed a literature review of the term "sarcopenia" in PubMed. Inclusion criteria were English language, original data, a clear and specific definition for diagnosing sarcopenia, and the analysis of sarcopenia's effect on a clinical outcome. A total of 283 studies met inclusion criteria. More than half of the included sarcopenia investigations were level IV studies (54.1%), while 43.1% provided level II evidence. Under one third (27.6%) of studies examined sarcopenia with regard to surgical outcomes. In terms of diagnostic criteria for…

The history of percutaneous coronary intervention (PCI) is marked by rapid technological advancements that have taken place over the past 40 years. After a period of balloon angioplasty, which was marred by risk of abrupt vessel closure and vessel recoil, balloon expandable metal alloy stents were the mainstay of PCI. The introduction of drug eluting stents (DES) targeted in-stent restenosis, a common mode of stent failure, and ushered in the current PCI era. Since the first generation of DES, advances in polymer science and stent design have advanced the field. The current generation of DES has thin struts, are highly deliverable, have biocompatible or absorbable polymers, and outstanding safety and efficacy profiles. In this review, we discuss the technological advancements in stent development, design, and construction, with an emphasis on balloon expandable stents. The aspects of stent properties, metal alloys, bioresorbable vascular scaffolds, drug elution, and polymers will be covered.

There is evidence to suggest that biological sex plays a critical role in memory function, with sex differentially influencing memory type. In this review, we detail the current evidence evaluating sex-specific effects on various memory types. We also discuss potential mechanisms that explain these sex-specific effects, which include sex differences in neuroanatomy, neurochemical differences, biological differences, and cognitive and affect-related differences. Central to this review, we also highlight that, despite the established sex differences in memory, there is little work directly comparing whether males and females have a differential exercise-induced effect on memory function. As discussed herein, such a differential effect is plausible given the clear sex-specific effects on memory, exercise response, and molecular mediators of memory. We emphasize that future work should be carefully powered to detect sex differences. Future research should also examine these potential exercise-related sex-specific effects for various memory types and exercise intensities and modalities.…

A small proportion of lean patients develop non-alcoholic fatty liver disease (NAFLD). We aimed to report the histological picture of lean NAFLD in comparison to overweight and obese NAFLD patients. Biopsy and clinical data from 466 patients diagnosed with NAFLD were stratified to groups according to body mass index (BMI): lean (BMI ≤ 25.0 kg/m², n confirmed to be appropriate = 74), overweight (BMI > 25.0 ≤ 30.0 kg/m², n = 242) and obese (BMI > 30.0 kg/m², n = 150). Lean NAFLD patients had a higher rate of lobular inflammation compared to overweight patients (12/74; 16.2% vs. 19/242; 7.9%; p = 0.011) but were similar to obese patients (25/150; 16.7%). Ballooning was observed in fewer overweight patients (38/242; 15.7%) compared to lean (19/74; 25.7%; p = 0.014) and obese patients (38/150; 25.3%; p = 0.006). Overweight patients had a lower rate of portal and periportal fibrosis (32/242; 13.2%) than lean (19/74; 25.7%; p = 0.019) and obese patients (37/150; 24.7%; p = 0.016). The rate of cirrhosis was higher in lean patients (6/74; 8.1%) compared to overweight (4/242; 1.7%; p = 0.010)…

Interstitial lung disease (ILD) and pulmonary fibrosis comprise a wide array of inflammatory and fibrotic lung diseases which are often confusing to general medicine and pulmonary physicians alike. In addition to the myriad of clinical and radiologic nomenclature used in ILD, histopathologic descriptors may be particularly confusing, and are often extrapolated to radiologic imaging patterns which may further add to the confusion. We propose that rather than focusing on precise histologic findings, focus should be on identifying an accurate etiology of ILD through a comprehensive and detailed medical history. Histopathologic patterns from lung biopsy should not be dismissed, but are often nonspecific, and overall treatment strategy and prognosis are likely to be determined more by the specific etiology of ILD rather than any particular histologic pattern. In this review, we outline a practical approach to common ILDs, highlight important aspects in obtaining an exposure history, clarify terminology and nomenclature, and discuss six common subgroups of ILD likely to be encountered by…

Evidence has recently emerged on the influence of gender on the immune system. In this systematic review and meta-analysis of phase III randomized clinical trials (RCTs), we explored the impact of gender on survival in patients with advanced cancer treated with immune checkpoint inhibitors (ICIs). We performed a comprehensive search of the literature updated to April 2018, including the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE. We extracted data on study characteristics and risk of bias in duplicate. Of 423 unique citations, 21 RCTs were included, inherently to 12,635 patients. Both males and females showed reduced risk of death associated with ICIs use (HR 0.73, p<0.001 and HR 0.77, p<0.001, respectively). Subgroup analyses by specific ICI showed similar OS in both genders for anti-PD-1/PDL-1. Anti-CTLA-4 use was associated with longer OS in men only (HR 0.77, p<0.012), with the exception of melanoma (in women, HR 0.80, p=0.006). PFS was longer in men than in women (HR 0.67, p<0.001 and HR 0.77, p=0.100, respectively). Conclusively, ICIs use was associated…

Irritable bowel syndrome (IBS) is one of the most common of all medical disorders worldwide and, while for some it represents no more than a nuisance, for others it imposes significant negative impacts on daily life and activities. IBS is a heterogeneous disorder and may well have a number of causes which may lie anywhere from the external environment to the contents of the gut lumen and from the enteric neuromuscular apparatus and the gut immune system to the central nervous system. Consequently, the paradigm of the gut-brain axis, which includes the participation of these various factors, has proven a useful model to assist clinicians and patients alike in understanding the genesis of symptoms in IBS. Now, given the widespread interest in the gut microbiome in health and disease, in general, reports of disordered enteric bacterial communities in IBS, and experimental data to indicate that components of the gut microbiota can influence brain morphology and function, as well as behavior and cognition, this concept has been extended to encompass the microbiota-gut-brain axis. The…

Cognitive frailty, defined as the presence of both frailty and cognitive impairment, is a risk factor for adverse events in older adults. However, prevalence rates of cognitive frailty are low (1.1⁻2.5%), so primary screening is unsuitable in community settings. The aim of the study was to examine whether a new definition of cognitive frailty, which was developed for primary screening, is useful to predict incident dementia in community-dwelling older adults. A total of 4570 older adults participated in the study (2326 women; average age, 71.9 ± 5.5 years). We defined physical frailty as the presence of ≥1 of the following symptoms: slow walking speed and muscle weakness. Cognitive impairment was defined as ≥1 symptom of cognitive impairment, indicated by an age- and education-adjusted score that was ≥1.5 standard deviations below the reference threshold in word list memory, attention, executive function, and processing speed tests. Cognitive frailty was defined as comorbid physical frailty and cognitive impairment. The incidence of dementia was determined using data collected by…

Obesity represents an abnormal fat accumulation resulting from energy imbalances. It represents a disease with heavy consequences on population health and society economy due to its related morbidities and epidemic proportion. Defining and classifying obesity and its related parameters of evaluation is the first challenge toward understanding this multifactorial health problem. Therefore, within this review we report selected illustrative examples of the underlying mechanisms beyond the obesity pathogenesis which is systemic rather than limited to fat accumulation. We also discuss the gut-brain axis and hormones as the controllers of energy homeostasis and report selected impacts of obesity on the key metabolic tissues. The concepts of "broken energy balance" is detailed as the obesity starting key step. Sleep shortage and psychological factors are also reported with influences on obesity development. Importantly, describing such mechanistic pathways would allow clinicians, biologists and researchers to develop and optimize approaches and methods in terms of diagnosis,…

BACKGROUND: In end-stage renal disease (ESRD), gut-derived uremic toxins play a crucial role in the systemic inflammation and oxidative stress promoting the excess morbidity and mortality. The biochemical derangement is in part a consequence of an insufficient generation of short-chain fatty acids (SCFA) due to the dysbiosis of the gut and an insufficient consumption of the fermentable complex carbohydrates. AIM OF THE STUDY: The primary end-point was to evaluate the potential efficacy of SCFA (specifically, sodium propionate (SP)) for patients on maintenance hemodialysis (MHD) on systemic inflammation. Secondary end-points included potential attenuation of oxidative stress markers, insulin resistance and production of gut-derived uremic toxins indoxyl sulfate and p-cresol sulfate, as well as health status after SP supplementation. STUDY DESIGN: We performed a single-center non-randomized pilot study in 20 MHD patients. They received the food additive SP with a daily intake of 2 × 500 mg in the form of capsules for 12 weeks. Pre-dialysis blood samples were taken at the beginning,…

Women affected by autoimmune diseases, organ transplantation, or neoplasia need to continue immunosuppressive treatment during pregnancy. In this setting, not only a careful planning of pregnancy, but also the choice of drugs is critical to preventing maternal complications and minimizing the fetal risks. Some immunosuppressive drugs are teratogenic and should be replaced even before the pregnancy, while other drugs need to be managed with caution to prevent fetal risks, including miscarriage, intrauterine growth restriction, prematurity, and low birth weight. In particular, the increasing use of biologic agents raises the question of their compatibility with reproduction. In this review we present data on the indication and safety in pregnancy of the most frequently used immunosuppressive drugs.

Cancer cachexia (CC), characterized by body weight loss and sarcopenia, contributes to over 20% of all cancer-related death. Approximately 80% of pancreatic cancer (PC) patients develop CC during disease progression. Pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α, have been correlated with CC; however, its prognostic significance remains unclear. In this study, serum levels of the CC-related cytokines were determined in normal donors and PC patients. IL-8 expression was assessed in PC tissue microarrays. The correlation of levels of each cytokine with disease progression, weight loss, and sarcopenia was calculated. The relationships among the baseline variables, CC, and IL-8 expression with disease progression were examined using univariate and multivariate analyses. Of these mentioned cytokines, only serum IL-8 level was elevated in the locally advanced group (n = 55) compared with the normal (n = 17) and resected groups (n = 55). Serum IL-8 level was positively correlated with CC status, weight loss, sarcopenia, but was…

The aim of this study was to determine the risk of infection in adults with inflammatory rheumatic diseases (IRDs) treated with methotrexate. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing methotrexate versus placebo in adults using MEDLINE, EMBASE, and CENTRAL databases from 1980 to August 2017. The primary outcome was the risk of infection associated with methotrexate therapy. We chose a random effect model to summarize adverse event outcomes as risk ratios (RRs) and related 95% confidence intervals (95% CI). Twelve RCTs (total patients 1146) met the inclusion criteria for our main analysis, and ten for risk of serious infection (total patients 906). Overall, methotrexate was associated with increased risk of infection in rheumatoid arthritis (RA) (RR: 1.25; 95% CI, 1.01⁻1.56; p = 0.04; I² = 0%), but not in other non-RA IRD populations. There was no increased risk of total infections (RR: 1.14; 95% CI, 0.98⁻1.34; p = 0.10; I² = 0%) or serious infections (RR: 0.76; 95% CI, 0.11⁻5.15; p = 0.78; I² = 0%) in all included IRDs.…

BACKGROUND: Cytoreductive surgery (CRS), followed by hyperthermic intraperitoneal chemotherapy (HIPEC), combines radical surgery with abdominal heated chemotherapy, constituting a multimodal treatment approach. Since clear standards for HIPEC conduct in colorectal carcinoma (CRC) are lacking, we aimed to provide a comprehensive structured survey. Data sources and study eligibility criteria: A systematic literature search was performed in PubMed, with keywords "HIPEC" and "colorectal cancer", according to established guidelines. Articles were systematically screened, selecting 87 publications complemented by 48 publications identified through extended search for subsequent synthesis and evaluation, extracting inter alia details on used drugs, dosage, temperature, exposure times, and carrier solutions. RESULTS: Compiled publications contained 171 reports on HIPEC conduct foremost with mitomycin C and oxaliplatin, but also other drugs and drug combinations, comprising at least 60 different procedures. We hence provide an overview of interconnections between HIPEC protocols, used drugs…

Hypertension is a common chronic cardiovascular disease (CVD). Early screening and diagnosis of hypertension plays a major role in its prevention and in the control of CVDs. Our study discusses the early screening of hypertension while using the morphological features of photoplethysmography (PPG). Numerous morphological features of PPG and its derivative waves were defined and extracted. Six types of feature selection methods were chosen to screen and evaluate these PPG morphological features. The optimal features were comprehensively analyzed in relation to the physiological processes of the cardiovascular circulatory system. Particularly, the intrinsic relation and physiological significance between the formation process of systolic blood pressure (SBP) and PPG morphology features were analyzed in depth. A variety of linear and nonlinear classification models were established for the comparison trials. The F1 scores for the normotension versus prehypertension, normotension and prehypertension versus hypertension, and normotension versus hypertension trials were 72.97%, 81.82%,…